Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease
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- Stephanie Bertram
- Institute of Virology, Hannover Medical School, Hannover, Germany
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- Ilona Glowacka
- Institute of Virology, Hannover Medical School, Hannover, Germany
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- Marcel A. Müller
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
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- Hayley Lavender
- Oxfabs, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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- Kerstin Gnirss
- Institute of Virology, Hannover Medical School, Hannover, Germany
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- Inga Nehlmeier
- German Primate Center, Göttingen, Germany
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- Daniela Niemeyer
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
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- Yuxian He
- Institute of Pathogen Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China
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- Graham Simmons
- Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, California
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- Christian Drosten
- Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
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- Elizabeth J. Soilleux
- Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom
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- Olaf Jahn
- Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany
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- Imke Steffen
- Institute of Virology, Hannover Medical School, Hannover, Germany
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- Stefan Pöhlmann
- Institute of Virology, Hannover Medical School, Hannover, Germany
Description
<jats:title>ABSTRACT</jats:title> <jats:p> The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in <jats:italic>cis</jats:italic> and <jats:italic>trans</jats:italic> , while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in <jats:italic>trans</jats:italic> . However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients. </jats:p>
Journal
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- Journal of Virology
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Journal of Virology 85 (24), 13363-13372, 2011-12-15
American Society for Microbiology
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Details 詳細情報について
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- CRID
- 1363951794711917056
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- ISSN
- 10985514
- 0022538X
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- Data Source
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- Crossref